The research objectives of this project are to investigate the chemical control of respiration and to apply existing and new knowledge of control of respiration to the investigation of patients with chronic obstructive pulmonary disease. Basic studies of ventilation during transient hypoxia and hypercapnia at the carotid bodies will be continued. These will consist of perfusion experiments in which forcing functions under open loop conditions are utilized in a control systems approach to the functional dissection of the respiratory control system. The mechanism of depression of the respiratory control system during oxygen administration in some patients with chronic obstructive pulmonary disease and carbon dioxide retention, but not in others with an apparently comparable degree of airway obstruction, hypoxemia and hypercapnia, still needs to be defined. The specific area to be investigated in this research is the alteration of cerebral metabolism of amino acids resulting from elevated blood and cerebrospinal fluid ammonia levels or facilitated diffusion of ammonia. The presence of abnormal concentrations of amino acids will be correlated with the ventilatory response of these patients when the hypoxic stimulus to thier peripheral chemoreceptors has been reduced or eliminated by oxygen administration.